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Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof....
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Special Issue "Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson"

A special issue of Receptors (ISSN 2813-2564).

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 4669

Special Issue Editor

Dr. Anders Strom

E-Mail Website
Guest Editor
Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX, USA
Interests: nuclear receptors; estrogen receptor signaling; estrogen receptor beta; cancer stem cells; prostate cancer; breast cancer

Special Issue Information

Dear Colleagues,

Recently, we passed 25-year mark since the discovery of the two important nuclear receptors LXRβ and Erβ. The publication of Professor Gustafsson’s paper (PNAS 14;92 (6) 2096-2100, 1995) where he described the cloning of the nuclear receptor OR-1, later renamed to LXRβ, was fundamental to understanding cholesterol homeostasis and its regulation, and has resulted in many publications from Professor Gustafsson and others. One year later, another nuclear receptor was cloned (PNAS 93 (12) 5925-5930, 1996). This was a second estrogen receptor and was named Erβ; it was a fundamental paradigm shift since all effects until then had been attributed to the only known estrogen receptor which was then renamed to ERα. The cloning of ERβ initiated much activity from individual researchers as well as from companies because of the potential new drug target for the treatment of diseases. Evaluation of ERβ as a drug target is still ongoing. In addition, Gustafsson has been involved in revealing the 3D structure of nuclear receptors, the binding of nuclear receptors to DNA, and the discovery of the steroid response element.

This Special Issue is focused on the role of nuclear receptors in health and disease. The Special Issue begins with a short review of Professor Gustafsson’s contribution to the field of nuclear receptors followed by original research articles and reviews on all aspects of nuclear receptors in health and disease.

Dr. Anders Strom
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Receptors is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • estrogen receptor beta
  • liver X receptor beta
  • nuclear receptors
  • steroid hormones

Published Papers (4 papers)

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Research

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Article
Estrogen Receptor β Isoforms Regulate Chemotherapy Resistance and the Cancer Stem Cell Population in Prostate Cancer Cells
by
Jessica H. Stevens
,
Ayesha Bano
,
Lamia Bensaoula
,
Anders M. Strom
and
Jan-Åke Gustafsson
Receptors 2023, 2(3), 176-190; https://doi.org/10.3390/receptors2030012 - 01 Aug 2023
Viewed by 573
Abstract
Estrogen receptor beta 1 (ERβ1) is a ligand-activated nuclear receptor, which has been shown to maintain tissue differentiation in the normal prostate, and regulate androgen response and increase expression of tumor suppressors in prostate cancer cell lines. There are three shorter isoforms of [...] Read more.
Estrogen receptor beta 1 (ERβ1) is a ligand-activated nuclear receptor, which has been shown to maintain tissue differentiation in the normal prostate, and regulate androgen response and increase expression of tumor suppressors in prostate cancer cell lines. There are three shorter isoforms of ERβ expressed in the human prostate, ERβ2, ERβ4, and ERβ5, which have already been implicated in chemotherapy resistance and disease progression, suggesting a possible oncogenic role. Their ligand-binding domain (LBD) is truncated, so they are unable to activate canonical ERβ1 signaling pathways; however, they were shown to participate in hypoxic signaling and to induce a gene expression signature associated with stemness and hypoxia. To elucidate the role of the truncated ERβ isoforms in prostate cancer, we created a knockout of all isoforms, as well as a truncation of the LBD, to remove the function of ERβ1. We showed that the removal of all isoforms leads to a decrease in the expression of cancer stem cell (CSC)-associated genes, decreased chemotherapy resistance, and a decrease in the CSC population, based on sphere formation ability and SORE6 (CSC reporter) activity, while removing the LBD function only had the opposite effect. Our results suggest a more aggressive phenotype in prostate cancer cell lines expressing ERβ variants. Full article
(This article belongs to the Special Issue Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson)
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Article
A Novel Liver X Receptor Inverse Agonist Impairs Cholesterol and Phospholipid Metabolism and Induces Apoptosis and Necroptosis in Pancreatic Ductal Adenocarcinoma Cells
by
Scott Widmann
,
Shivangi Srivastava
and
Chin-Yo Lin
Receptors 2023, 2(1), 34-46; https://doi.org/10.3390/receptors2010003 - 01 Feb 2023
Cited by 1 | Viewed by 1347
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and few effective treatments. A growing area of cancer therapeutics seeks to exploit the metabolic dysregulation of cancer cells, such as glucose, amino acid, and fatty acid metabolism, to selectively [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and few effective treatments. A growing area of cancer therapeutics seeks to exploit the metabolic dysregulation of cancer cells, such as glucose, amino acid, and fatty acid metabolism, to selectively target malignant cells. As ligand-dependent transcription factors and critical regulators of metabolism, liver X receptors (LXRs) are amenable to small-molecule targeting for such purposes. We have profiled the transcriptomic, metabolomic, and cytotoxic effects of a newly discovered small-molecule LXR modulator, GAC0003A4 (3A4), in PDAC cell lines. On the transcriptomic level, marked changes in gene expression were observed, including downregulation of LXR target genes and pathways. Gene set enrichment analysis determined downregulation of several metabolic pathways, such as fatty acid and cholesterol metabolism, while upregulated pathways involved TNFα/NF-κB and other stress-induced processes. Metabolomic analyses revealed altered metabolites in several pathways, the most enriched categories being lipids and amino acid metabolites, while phospholipids and sphingolipids, including ceramides, were also found to be significantly altered. Insights from transcriptomic and metabolomic studies helped guide the determination of alterations in cholesterol and ceramides as integral to the antiproliferative mechanisms of 3A4. Additionally, a concurrent programmed cell death mechanism involving apoptosis and necroptosis was shown to be activated. These studies provide novel insights into the effects of LXR modulation on gene expression, metabolism, and cell death induction in PDAC cells. The metabolic and cytotoxic effects of LXR modulation on the PDAC cell lines used in this study could also aid in the design and application of drugs to target other refractory cancers. Full article
(This article belongs to the Special Issue Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson)
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Review

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Review
Estrogen Receptor Knockout Mice and Their Effects on Fertility
by
Ivan Nalvarte
and
Per Antonson
Receptors 2023, 2(1), 116-126; https://doi.org/10.3390/receptors2010007 - 07 Mar 2023
Cited by 1 | Viewed by 1584
Abstract
Estrogens play a crucial role in sexual development and fertility as well as many other physiological processes, and it is estrogen receptors that mediate the physiological responses. To study the role of the estrogen receptors in these processes, several genetic mouse models have [...] Read more.
Estrogens play a crucial role in sexual development and fertility as well as many other physiological processes, and it is estrogen receptors that mediate the physiological responses. To study the role of the estrogen receptors in these processes, several genetic mouse models have been developed using different strategies, which also in some cases yield different results. Here, we summarize the models that have been made and their impact on fertility in relation to known cases of human estrogen receptor mutations. Full article
(This article belongs to the Special Issue Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson)
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Other

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Opinion
From Antibodies to Crystals: Understanding the Structure of the Glucocorticoid Receptor and Related Proteins
by
Iain J. McEwan
Receptors 2023, 2(3), 166-175; https://doi.org/10.3390/receptors2030011 - 03 Jul 2023
Viewed by 557
Abstract
The steroid/thyroid hormone or nuclear receptor superfamily is quickly approaching its 40th anniversary. During this period, we have seen tremendous progress being made in our understanding of the mechanisms of action of these physiologically important proteins in the field of health and disease. [...] Read more.
The steroid/thyroid hormone or nuclear receptor superfamily is quickly approaching its 40th anniversary. During this period, we have seen tremendous progress being made in our understanding of the mechanisms of action of these physiologically important proteins in the field of health and disease. Critical to this has been the insight provided by ever more detailed structural examination of nuclear receptor proteins and the complexes they are responsible for assembling on DNA. In this article, I will focus on the contributions made by Jan-Åke Gustafsson and colleagues at the Karolinska Institute (Sweden) and, more recently, the University of Houston (USA), to this area of nuclear receptor research. Full article
(This article belongs to the Special Issue Nuclear Receptors: Honorary Special Issue Commemorating the Work of Prof. Jan-Åke Gustafsson)
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